Bariatric surgery induces pancreatic cell transdifferentiation as indicated by single-cell transcriptomics in Zucker diabetic rats

单细胞转录组学研究表明减肥手术可诱导 Zucker 糖尿病大鼠胰腺细胞转分化

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作者:Yongjun Liang, Jason Widjaja, Jiawei Sun, Mengyi Li, Zhengdong Qiao, Ting Cao, Yueqian Wang, Xiong Zhang, Zhongtao Zhang, Yan Gu, Peng Zhang, Jianjun Yang

Aims

Bariatric surgery

Conclusions

For the first time, using the single-cell transcriptome map of ZDF rats, we reported a comprehensive characterization of the heterogeneity and differentiation of pancreatic endocrinal cells after bariatric surgery, which may contribute to the underlying mechanisms. Further studies will be needed to elucidate these results.

Methods

Male, 8-week-old Zucker diabetic fatty (ZDF) rats with obesity and diabetes phenotypes were randomized into sleeve gastrectomy (Sleeve, n = 9), Roux-en-Y gastric bypass (RYGB, n = 9), and Sham (n = 7) groups. Two weeks after surgery, the pancreas specimen was further analyzed using single-cell RNA-sequencing technique.

Results

Two weeks after surgery, compared to the Sham group, the metabolic parameters including fasting plasma glucose, plasma insulin, and oral glucose tolerance test values were dramatically improved after RYGB and Sleeve procedures (p < .05) as predicted. In addition, RYGB and Sleeve groups increased the proportion of pancreatic β cells and reduced the ratio of α cells. Two multiple hormone-expressing cells were identified, the Gcg+/Ppy + and Ins+/Gcg+/Ppy + cells. The pancreatic Ins+/Gcg+/Ppy + cells were defined for the first time, and further investigation indicates similarities with α and β cells, with unique gene expression patterns, which implies that pancreatic cell transdifferentiation occurs following bariatric surgery. Conclusions: For the first time, using the single-cell transcriptome map of ZDF rats, we reported a comprehensive characterization of the heterogeneity and differentiation of pancreatic endocrinal cells after bariatric surgery, which may contribute to the underlying mechanisms. Further studies will be needed to elucidate these results.

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